Is Circulating Vitamin D Status Associated with the Risk of Venous Thromboembolism? A Meta-Analysis of Observational Studies.

BACKGROUND: Although vitamin D is antithrombotic, associations between serum vitamin D status and the risk of venous thromboembolism (VTE) remain inconsistent. METHODS: We searched the EMBASE, MEDLINE, Cochrane Library, and Google Scholar databases from inception to June 2022 to identify observational studies examining associations between vitamin D status and VTE risk in adults. The primary outcome presented as odds ratio (OR) or hazard ratio (HR) was the association of vitamin D levels with the risk of VTE. Secondary outcomes included the impacts of vitamin D status (i.e., deficiency or insufficiency), study design, and the presence of neurological diseases on the associations. RESULTS: Pooled evidence from a meta-analysis of sixteen observational studies, including 47648 individuals published from 2013 to 2021, revealed a negative relationship between vitamin D levels and the risk of VTE either based on OR (1.74, 95% confidence interval (CI): 1.37 to 2.20, p < 0.00001; I2 = 31%, 14 studies, 16074 individuals) or HR (1.25, 95% CI: 1.07 to 1.46, p = 0.006; I2 = 0%, 3 studies, 37,564 individuals). This association remained significant in subgroup analyses of the study design and in the presence of neurological diseases. Compared to individuals with normal vitamin D status, an increased risk of VTE was noted in those with vitamin D deficiency (OR = 2.03, 95% CI: 1.33 to 3.11) but not with vitamin D insufficiency. CONCLUSIONS: This meta-analysis demonstrated a negative association between serum vitamin D status and the risk of VTE. Further studies are required to investigate the potential beneficial effect of vitamin D supplementation on the long-term risk of VTE.

A meta-analysis of randomized clinical trials on the impact of oral vitamin C supplementation on first-year outcomes in orthopedic patients.

This meta-analysis aimed at investigating the impact of oral vitamin C supplementation on the post-procedural recovery of orthopedic patients, including functional outcomes and complex regional pain syndrome type I (CRPS I). Literature search using the Medline, Cochrane Library, and Embase databases from inception till March 2021 identified seven eligible randomized controlled trials with 1,361 participants. Forest plot revealed no significant difference in the functional outcomes at 6-12 months [standardized mean difference (SMD) = -0.00, 95% CI - 0.19 to 0.18, 467 patients], risk of overall complications (RR = 0.98, 95% CI 0.68 to 1.39, 426 patients), and pain severity at 3-6 months (SMD = - 0.18, 95% CI - 0.49 to 0.12, 486 patients) between patients with and without oral vitamin C supplementation. Pooled analysis showed that vitamin C treatment reduced the risk of CRPS I regardless of dosage (RR = 0.46, 95% CI 0.25 to 0.85, 1143 patients). In conclusion, the current meta-analysis demonstrated that oral vitamin C supplementation may reduce the risk of complex regional pain syndrome type I but did not improve the functional outcomes in orthopedic patients. Nevertheless, because of the small number of trials included in the present study, further large-scale clinical studies are warranted to support our findings.

The Effect of Perioperative Vitamin C on Postoperative Analgesic Consumption: A Meta-Analysis of Randomized Controlled Trials.

Because the analgesic effect of vitamin C against acute pain remains poorly addressed, this meta-analysis aimed at investigating its effectiveness against acute postoperative pain. A total of seven randomized controlled trials with placebo/normal controls were identified from PubMed, Cochrane Library, Medline, Google Scholar, and Embase databases. Pooled analysis showed a lower pain score (standardized mean difference (SMD) = -0.68, 95% CI: -1.01 to -0.36, p < 0.0001; I2 = 57%) and a lower morphine consumption (weighted mean difference (WMD) = -2.44 mg, 95% CI: -4.03 to -0.86, p = 0.003; I2 = 52%) in the vitamin group than that in the placebo group within postoperative 1-2 h. At postoperative 24 h, a lower pain score (SMD = -0.65, 95% CI: -1.11 to -0.19, p = 0.005; I2 = 81%) and lower morphine consumption (WMD = -6.74 mg, 95% CI: -9.63 to -3.84, p < 0.00001; I2 = 85%) were also noted in the vitamin group. Subgroup analyses demonstrated significant reductions in pain severity and morphine requirement immediately (1-2 h) and 24 h after surgery for patients receiving intravenous vitamin C but not in the oral subgroup. These findings showed significant reductions in pain score and opioid requirement up to postoperative 24 h, respectively, suggesting the effectiveness of perioperative vitamin C use. Further large-scale trials are warranted to elucidate its optimal intravenous dosage and effectiveness against chronic pain in the postoperative pain control setting.

Patient characteristics and analgesic efficacy of antiviral therapy in postherpetic neuralgia.

Postherpetic neuralgia (PHN) is the most common complication of shingles caused by reactivation of varicella zoster virus (VZV). Management of PHN is often suboptimal while using current conventional treatments. Antiviral therapy was used to reduce PHN-associated pain in two small trials which showed conflicting results. We hypothesize the analgesic efficacy of antiviral therapy on PHN is affected by patient characteristics including pathophysiology of the participants and serum vitamin D levels. Pathophysiology of PHN includes neuronal excitability and chronic VZV ganglionitis (persistent active VZV infection in ganglions). VZV-DNA positivity or a positive IgG coupled with a positive IgM indicates recent or current VZV infection. Positive VZV-DNA or IgG/IgM tests are used to confirm whether the patients experience chronic VZV ganglionitis. Antiviral therapy decreases pain in PHN patients with chronic VZV ganglionitis; whereas, antiviral therapy shows no effects in PHN patients with negative VZV-DNA or IgM. Vitamin D is a natural antiviral mediator. Studies show a high prevalence of vitamin D deficiency in hepatitis B/C virus-infected patients. Serum vitamin D levels and vitamin D supplementation are factors which affect the antiviral efficacy on hepatitis B/C virus infection. Serum 25-OHD levels of hospitalized patients with shingles were significantly lower compared to healthy controls. Accordingly, PHN patient may have a high prevalence of vitamin D deficiency which negatively affects the antiviral efficacy. Vitamin D supplementation may improve the antiviral efficacy on PHN. Future trials regarding antiviral therapy on PHN should consider patient characteristics and should be conducted among different subgroups of PHN patients.

Treatment of Postherpetic Neuralgia With Intravenous Administration of Zinc Sulfate: A Case Report.

Gabapentinoids (gabapentin and pregabalin) are first-line drugs for postherpetic neuralgia (PHN), but some PHN patients have inadequate therapeutic response. Zinc deficiency has been identified as a risk factor for PHN. Zinc can alleviate pain through binding to Ca(v)3.2 T-channels and N-methyl-D-aspartate receptors. Mechanisms of gabapentinoids on neuropathic pain include inhibiting N-methyl-D-aspartate receptors and calcium channels. The aforementioned findings provide a molecular pain-relieving basis for zinc supplements as an add-on therapy to pregabalin. We report 2 zinc-deficient PHN patients who received zinc sulfate intravenously as an add-on therapy to pregabalin and responded well.

The antinociceptive and anti-inflammatory effects of five depot formulations of ketorolac propyl ester in rats.

BACKGROUND: Ketorolac is a potent nonsteroidal anti-inflammatory drug. Recently, a ketorolac prodrug, ketorolac propyl ester, was synthesized in our laboratory. The aim of the study was to evaluate the antinociceptive and anti-inflammatory effects of ketorolac propyl ester in five depot formulations. The vehicles used in these formulations were injectable vegetable oils, i.e., sesame oil, peanut oil, soybean oil, castor oil, and cottonseed oil. The traditional therapentic form of ketorolac tromethamine in saline was used as control. METHODS: Six studies were carried out to test the antinociceptive and anti-inflammatory effects of intramuscular ketorolac tromethamine (in saline) and its propyl ester (in five depot formulations) 240 micromol/kg on Sprague-Dawley rats treated with intraplantar carrageenin. RESULTS: Ketorolac tromethamine (in saline) produced an 8 h duration of action on both antinociception and anti-inflammation, whereas ketorolac propyl ester in five oily vehicles produced 54- to 78-h durations of actions in both antinociception and anti-inflammation. Ketorolac propyl ester in cottonseed oil produced a duration of action of 78h in both antinociception and anti-inflammation. CONCLUSIONS: All five depot formulations of ketorolac propyl ester produced longer durations of antinociceptive and anti-inflammatory effects.